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Metabolic and proteomic signatures of type 2 diabetes subtypes in an Arab population

Author

Listed:
  • Shaza B. Zaghlool

    (Weill Cornell Medicine-Qatar)

  • Anna Halama

    (Weill Cornell Medicine-Qatar)

  • Nisha Stephan

    (Weill Cornell Medicine-Qatar)

  • Valborg Gudmundsdottir

    (University of Iceland
    Icelandic Heart Association)

  • Vilmundur Gudnason

    (University of Iceland
    Icelandic Heart Association)

  • Lori L. Jennings

    (Novartis Institutes for Biomedical Research)

  • Manonanthini Thangam

    (Lund University)

  • Emma Ahlqvist

    (Lund University)

  • Rayaz A. Malik

    (Weill Cornell Medicine-Qatar)

  • Omar M. E. Albagha

    (Hamad Bin Khalifa University, Education City
    University of Edinburgh)

  • Abdul Badi Abou‑Samra

    (Hamad Medical Corporation)

  • Karsten Suhre

    (Weill Cornell Medicine-Qatar)

Abstract

Type 2 diabetes (T2D) has a heterogeneous etiology influencing its progression, treatment, and complications. A data driven cluster analysis in European individuals with T2D previously identified four subtypes: severe insulin deficient (SIDD), severe insulin resistant (SIRD), mild obesity-related (MOD), and mild age-related (MARD) diabetes. Here, the clustering approach was applied to individuals with T2D from the Qatar Biobank and validated in an independent set. Cluster-specific signatures of circulating metabolites and proteins were established, revealing subtype-specific molecular mechanisms, including activation of the complement system with features of autoimmune diabetes and reduced 1,5-anhydroglucitol in SIDD, impaired insulin signaling in SIRD, and elevated leptin and fatty acid binding protein levels in MOD. The MARD cluster was the healthiest with metabolomic and proteomic profiles most similar to the controls. We have translated the T2D subtypes to an Arab population and identified distinct molecular signatures to further our understanding of the etiology of these subtypes.

Suggested Citation

  • Shaza B. Zaghlool & Anna Halama & Nisha Stephan & Valborg Gudmundsdottir & Vilmundur Gudnason & Lori L. Jennings & Manonanthini Thangam & Emma Ahlqvist & Rayaz A. Malik & Omar M. E. Albagha & Abdul Ba, 2022. "Metabolic and proteomic signatures of type 2 diabetes subtypes in an Arab population," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-34754-z
    DOI: 10.1038/s41467-022-34754-z
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    References listed on IDEAS

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    1. Anna Halama & Shaza Zaghlool & Gaurav Thareja & Sara Kader & Wadha Al Muftah & Marjonneke Mook-Kanamori & Hina Sarwath & Yasmin Ali Mohamoud & Nisha Stephan & Sabine Ameling & Maja Pucic Baković & Jan, 2024. "A roadmap to the molecular human linking multiomics with population traits and diabetes subtypes," Nature Communications, Nature, vol. 15(1), pages 1-23, December.

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